Biomimetic Design and Construction of an Artificial Lung

本项目的最终目标是开发人工肺辅助装置技术，用于治疗急、慢性 肺衰竭慢性肺病是美国第三大死亡原因，超过了 只有心脏病和癌症目前，对于慢性病， 慢性阻塞性肺疾病（COPD），而不是肺移植，以及严重缺乏 捐赠器官限制了这种方法，使大多数患者依赖家庭氧疗。急性病 例如成人呼吸窘迫综合征（ARDS），通常需要机械通气， 并发症和死亡率仍然很高。替代品，如ExtraCorpus膜式氧合器 （ECMO）治疗只能在有限的时间内使用，需要高水平的抗凝治疗， 许多操作复杂性。人工肺的技术进步迫在眉睫 器械，包括器械的简化和延长使用，减少对抗凝的需求， 以紧凑的形式提供低血量的气体传输速率。在这里，我们提出了一个探索性的 生物工程研究补助金，用于开发生物人工肺技术， 仿生设计原理和微制造技术，以构建可扩展的呼吸辅助架构 能够在小而紧凑的结构中进行高水平的气体输送。成功开发A 生物人工肺将需要几个关键要素，其中许多尚未实现，因为 由于制造技术的限制，模仿自然肺部生理机能存在困难。具体目标 这项建议的目的是针对这些元素，包括设计一个仿生结构的能力， 小的预充体积和高水平的气体渗透性，并建立内皮化的 微血管网络，以支持在不存在抗凝剂的情况下无凝血的平稳血流。 这些目标与未来的临床目标一致，包括为患者提供长期治疗的能力。 功能性呼吸辅助装置，不需要大量抗凝，可在 可穿戴或潜在的可植入形式。为了实现这些目标，我们的目标是：1）生成一种仿生 设计并利用微制造技术构建包含微血管的人工肺模块 2）在血管内皮细胞中建立内皮化微流控网络 室和测定生物人工肺构建物的气体运输和血流凝固性质。

The ultimate goal of this project is to develop artificial lung assist device technology to treat acute and chronic pulmonary failure. Chronic lung disease is the third-leading cause of death in the United States, exceeded only by heart disease and cancer. Currently there are no long-term solutions for chronic diseases such as Chronic Obstructive Pulmonary Disease (COPD) other than lung transplantation, and a severe shortage of donor organs limits this approach, leaving most patients relying on home oxygen therapy. For acute illnesses such as Adult Respiratory Distress Syndrome (ARDS), mechanical ventilation is typically required, and complications and mortality remain very high. Alternatives such as ExtraCorporeal Membrane Oxygenator (ECMO) therapy can only be used for a limited duration, require high levels of anticoagulation and involve numerous operational complexities. There is an urgent need for technological advances in artificial lung devices, including simplification and extended use of devices, a reduced need for anticoagulation, and high gas transfer rates in a compact format with low blood volumes. Here we propose an Exploratory Bioengineering Research Grant to pursue the development of technology for a bioartificial lung, based on biomimetic design principles and microfabrication technology to build scalable respiratory assist architectures capable of high levels of gas transport in a small and compact structure. Successful development of a bioartificial lung will require several critical elements, many of which have not been realized because of difficulties in mimicking natural lung physiology due to limitations in fabrication technology. The specific aims of this proposal are directed towards these elements, including the ability to design a biomimetic structure with small priming volume and high levels of gas permeability, and the establishment of an endothelialized microvascular network to support smooth blood flow without clotting in the absence of anticoagulative agents. These goals are consistent with future clinical targets including the ability to provide patients with long-term functional respiratory assist devices that do not require extensive anticoagulation and that can be enabled in a wearable or potentially implantable format. To accomplish these goals, we aim 1) To generate a biomimetic design and utilize microfabrication technology to construct an artificial lung module comprising microvascular networks and gas-permeable membranes, and 2) To establish endothelialized microfluidic network in vascular chamber and determine gas transport and blood flow coagulation properties of bioartificial lung construct.